tbuckley/cabot-search huggingface dataset:
Risks of Mortality and Airflow Limitation in Japanese Individuals with Preserved Ratio Impaired Spirometry
Authors: Yasuyoshi Washio, Satoko Sakata, Satoru Fukuyama, Takanori Honda, Keiko Kan-o, Mao Shibata, Jun Hata, Hiromasa Inoue, Takanari Kitazono, Koichiro Matsumoto, Toshiharu Ninomiya
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

Rationale: Several Western studies have reported that participants with preserved ratio impaired spirometry (PRISm) have higher risks of airflow limitation (AFL) and death. However, evidence in East Asian populations is limited. Objectives: To investigate the relationship between PRISm and the risks of death and incident AFL in a Japanese population. Methods: A total of 3,032 community-dwelling Japanese participants aged ⩾40 years were seen in follow-up for a median of 5.3 years by annual spirometry examinations. Participants were classified into lung function categories at baseline as follows: normal spirometry (FEV1/FVC ⩾0.70 and FEV1 ⩾80% predicted), PRISm (⩾0.70 and <80%), AFL Global Initiative for Chronic Obstructive Lung Disease 1 (<0.70 and ⩾80%), and AFL Global Initiative for Chronic Obstructive Lung Disease 2–4 (<0.70 and <80%). Hazard ratios (HRs) and their 95% confidence intervals were computed using a Cox proportional hazards model. Measurements and Main Results: During the follow-up period, 131 participants died, 22 of whom died of cardiovascular disease, and 218 participants developed AFL. When examining the prognosis of each baseline lung function category, participants with PRISm had higher risks of all-cause death (HR, 2.20; 95% confidence interval, 1.35–3.59) and cardiovascular death (HR, 4.07; 1.07–15.42) than those with normal spirometry after adjusting for confounders. Moreover, the multivariable-adjusted risk of incident AFL was greater in participants with PRISm than in those with normal spirometry (HR, 2.48; 1.83–3.36). Conclusions: PRISm was associated with higher risks of all-cause and cardiovascular death and a greater risk of the development of AFL in a Japanese community.
The Spectrum of Valvular Heart Disease and the Importance of “Mild”
Authors: Rishi Puri, Iryna Dykun, Ankur Kalra
Journal: JAMA Network Open (2022)

Kunihiro Matsushita, MD, PhD; Yumin Gao, ScM; Jonathan Rubin, MD, MHS; Ajay J. Kirtane, MD, SM; Susheel Kodali, MD; Elizabeth Selvin, PhD, MPH; Alvaro Alonso, MD, PhD; Martin B. Leon, MD; Scott D. Solomon, MD; Josef Coresh, MD, PhD; Ervin R. Fox, MD; Amil M. Shah, MD, MPH
The unbearable limitations of solo science: Team science as a path for more rigorous and relevant research
Authors: Alison Ledgerwood, Cynthia Pickett, Danielle Navarro, Jessica D. Remedios, Neil A. Lewis
Journal: Behavioral and Brain Sciences (2022)

Abstract Both early social psychologists and the modern, interdisciplinary scientific community have advocated for diverse team science. We echo this call and describe three common pitfalls of solo science illustrated by the target article. We discuss how a collaborative and inclusive approach to science can both help researchers avoid these pitfalls and pave the way for more rigorous and relevant research.
Strengthening US Food Policies and Programs to Promote Equity in Nutrition Security: A Policy Statement From the American Heart Association
Authors: Anne N. Thorndike, Christopher D. Gardner, Katherine Bishop Kendrick, Hilary K. Seligman, Amy L. Yaroch, Aldrin V. Gomes, Kendra N. Ivy, Stephanie Scarmo, Caree Jackson Cotwright, Marlene B. Schwartz
Journal: Circulation (2022)

Nutritionally inadequate dietary intake is a leading contributor to chronic cardiometabolic diseases. Differences in dietary quality contribute to socioeconomic and racial and ethnic health disparities. Food insecurity, a household-level social or economic condition of limited access to sufficient food, is a common cause of inadequate dietary intake. Although US food assistance policies and programs are designed to improve food security, there is growing consensus that they should have a broader focus on nutrition security. In this policy statement, we define nutrition security as an individual or household condition of having equitable and stable availability, access, affordability, and utilization of foods and beverages that promote well-being and prevent and treat disease. Despite existing policies and programs, significant gaps remain for achieving equity in nutrition security across the life span. We provide recommendations for expanding and improving current food assistance policies and programs to achieve nutrition security. These recommendations are guided by several overarching principles: emphasizing nutritional quality, improving reach, ensuring optimal utilization, improving coordination across programs, ensuring stability of access to programs across the life course, and ensuring equity and dignity for access and utilization. We suggest a critical next step will be to develop and implement national measures of nutrition security that can be added to the current US food security measures. Achieving equity in nutrition security will require coordinated and sustained efforts at the federal, state, and local levels. Future advocacy, innovation, and research will be needed to expand existing food assistance policies and programs and to develop and implement new policies and programs that will improve cardiovascular health and reduce disparities in chronic disease.
Emerging cases of acute hepatitis of unknown origin in children amid the ongoing COVID-19 pandemic: Needs attention – Correspondence
Authors: Ranjan K. Mohapatra, Venkataramana Kandi, Hardeep Singh Tuli, Sarika Verma, Sandip Chakraborty, Ali A. Rabaan, Chiranjib Chakraborty, Kuldeep Dhama
Journal: International Journal of Surgery (2022)
Abstract IA013: Genetic heterogeneity and tumor microenvironment in glioblastoma
Authors: Kacper A. Walentynowicz, Dalit Engelhardt, Shreya Yadav, Ugoma Onubogu, Roberto Salatino, Cristina Vincentelli, Thomas O. McDonald, Franziska Michor, Michalina Janiszewska
Journal: Cancer Research (2022)

Abstract Glioblastoma (GBM), the most aggressive brain tumor, remains an unmet medical need. Despite aggressive chemotherapy, radiation and surgery, only 5.6% of patients survive beyond 5 years post-diagnosis. Targeted approaches have not been successful in this tumor type due to the extreme heterogeneity of GBM. Mosaic amplification of oncogenes suggests that multiple genetically distinct clones are present in each tumor. However, little is known about how different subpopulations of GBM cells interact with each other or with the surrounding tumor microenvironment (TME). To address this, we employed spatial protein profiling coupled with single-cell spatial maps of fluorescence in situ hybridization (FISH) for key oncogenes frequently amplified in GBM. Our analysis spanned 3-4 areas from 17 formalin-fixed paraffin-embedded (FFPE) GBM cases, 96 sub-regions of interest and total of 35,843 single nuclei. Digital spatial profiling for 79 protein markers associated with GBM biology, TME and neurobiology revealed high intra-tumor variability of vasculature, between distinct regions of the same tumor biopsy. The single-cell FISH signal quantification allowed us to classify tumors based on the relative frequency of cells harboring co-occurring of EGFR and CDK4 amplifications. Tumors with low odds ratio for EGFR and CDK4 co-amplification in a cell had a significantly higher EGFR copy number in cells harboring this amplification. Cell-to-cell variation in EGFR copy number was also much higher in these tumors, suggesting a possibility for extrachromosomal origin of this amplification. Interestingly, the tumors with high frequency of cells harboring co-amplification of EGFR and CDK4 exhibit higher infiltration by CD163+ immunosuppressive macrophages. Our results suggest that high throughput assessment of genomic alterations at the single cell level could provide a measure for predicting the immune state of GBM. Citation Format: Kacper A. Walentynowicz, Dalit Engelhardt, Shreya Yadav, Ugoma Onubogu, Roberto Salatino, Cristina Vincentelli, Thomas O. McDonald, Franziska Michor, Michalina Janiszewska. Genetic heterogeneity and tumor microenvironment in glioblastoma [abstract]. In: Proceedings of the AACR Special Conference on the Evolutionary Dynamics in Carcinogenesis and Response to Therapy; 2022 Mar 14-17. Philadelphia (PA): AACR; Cancer Res 2022;82(10 Suppl):Abstract nr IA013.
Systematic analysis of nutrigenomic effects of polyphenols related to cardiometabolic health in humans – Evidence from untargeted mRNA and miRNA studies
Authors: Tatjana Ruskovska, Irena Budić-Leto, Karla Fabiola Corral-Jara, Vladimir Ajdžanović, Anna Arola-Arnal, Francisca Isabel Bravo, Georgia-Eirini Deligiannidou, Jaroslav Havlik, Milkica Janeva, Elena Kistanova, Christos Kontogiorgis, Irena Krga, Marika Massaro, Marko Miler, Hicham Harnafi, Verica Milosevic, Christine Morand, Egeria Scoditti, Manuel Suárez, David Vauzour, Dragan Milenkovic
Journal: Ageing Research Reviews (2022)
Translational in vitro and in vivo PKPD modelling for apramycin against Gram-negative lung pathogens to facilitate prediction of human efficacious dose in pneumonia
Authors: Vincent Aranzana-Climent, Diarmaid Hughes, Sha Cao, Magdalena Tomczak, Malgorzata Urbas, Dorota Zabicka, Carina Vingsbo Lundberg, Jon Hansen, Johan Lindberg, Sven N. Hobbie, Lena E. Friberg
Journal: Clinical Microbiology and Infection (2022)

New drugs and methods to efficiently fight carbapenem-resistant gram-negative pathogens are sorely needed. In this study, we characterized the preclinical pharmacokinetics (PK) and pharmacodynamics of the clinical stage drug candidate apramycin in time kill and mouse lung infection models. Based on in vitro and in vivo data, we developed a mathematical model to predict human efficacy.Three pneumonia-inducing gram-negative species Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae were studied. Bactericidal kinetics were evaluated with time-kill curves; in vivo PK were studied in healthy and infected mice, with sampling in plasma and epithelial lining fluid after subcutaneous administration; in vivo efficacy was measured in a neutropenic mouse pneumonia model. A pharmacokinetic-pharmacodynamic model, integrating all the data, was developed and simulations were performed.Good lung penetration of apramycin in epithelial lining fluid (ELF) was shown (area under the curve (AUC)ELF/AUCplasma = 88%). Plasma clearance was 48% lower in lung infected mice compared to healthy mice. For two out of five strains studied, a delay in growth (∼5 h) was observed in vivo but not in vitro. The mathematical model enabled integration of lung PK to drive mouse PK and pharmacodynamics. Simulations predicted that 30 mg/kg of apramycin once daily would result in bacteriostasis in patients.Apramycin is a candidate for treatment of carbapenem-resistant gram-negative pneumonia as demonstrated in an integrated modeling framework for three bacterial species. We show that mathematical modelling is a useful tool for simultaneous inclusion of multiple data sources, notably plasma and lung in vivo PK and simulation of expected scenarios in a clinical setting, notably lung infections.
Short-Term Outcomes After Myopericarditis Related to COVID-19 Vaccination
Authors: Manan Pareek, Jeremy Steele, Jeremy Asnes, Lauren A. Baldassarre, Linda R. Casale, Nihar R. Desai, Robert W. Elder, Erin Faherty, Ian Ferguson, Robert F. Fishman, Zaniar Ghazizadeh, Laura R. Glick, E. Kevin Hall, Rohan Khera, Damianos G. Kokkinidis, Jennifer M. Kwan, Jamieson O’Marr, Adam Schussheim, Edward Tuohy, Yanting Wang, Erica S. Spatz, Daniel Jacoby, Edward J. Miller
Journal: JACC. Cardiovascular imaging (2022)
Characteristics of children ≤36 months of age with DIPG: A report from the international DIPG registry
Authors: Allison L Bartlett, Adam Lane, Brooklyn Chaney, Nancy Yanez Escorza, Katie Black, Anne Cochrane, Jane Minturn, Ute Bartels, Kathy Warren, Jordan Hansford, David Ziegler, Blanca Diez, Stewart Goldman, Roger Packer, Mark Kieran, Mariko DeWire-Schottmiller, Craig Erker, Michelle Monje-Deisseroth, Lars Wagner, Carl Koschmann, Kathleen Dorris, Chie-Schin Shih, Tim Hassall, Yvan Samson, Paul Fisher, Stacie S Wang, Karen Tsui, Gustavo Sevlever, Xiaoting Zhu, Phillip Dexheimer, Anthony Asher, Christine Fuller, Rachid Drissi, Blaise Jones, James Leach, Maryam Fouladi
Journal: Neuro-Oncology (2022)

Children ≤36 months with diffuse intrinsic pontine glioma (DIPG) have increased long-term survival (LTS, overall survival (OS) ≥24 months). Understanding distinguishing characteristics in this population is critical to improving outcomes.Patients ≤36 months at diagnosis enrolled on the International DIPG Registry (IDIPGR) with central imaging confirmation were included. Presentation, clinical course, imaging, pathology and molecular findings were analyzed.Among 1183 patients in IDIPGR, 40 were eligible (median age: 29 months). Median OS was 15 months. Twelve patients (30%) were LTS, 3 (7.5%) very long-term survivors ≥5 years. Among 8 untreated patients, median OS was 2 months. Patients enrolled in the registry but excluded from our study by central radiology review or tissue diagnosis had median OS of 7 months. All but 1 LTS received radiation. Among 32 treated patients, 1-, 2-, 3-, and 5-year OS rates were 68.8%, 31.2%, 15.6% and 12.5%, respectively. LTS had longer duration of presenting symptoms (P = .018). No imaging features were predictive of outcome. Tissue and genomic data were available in 18 (45%) and 10 patients, respectively. Among 9 with known H3K27M status, 6 had a mutation.Children ≤36 months demonstrated significantly more LTS, with an improved median OS of 15 months; 92% of LTS received radiation. Median OS in untreated children was 2 months, compared to 17 months for treated children. LTS had longer duration of symptoms. Excluded patients demonstrated a lower OS, contradicting the hypothesis that children ≤36 months with DIPG show improved outcomes due to misdiagnosis.
Effects of exercise training on the cognitive function of older adults with different types of dementia: a systematic review and meta-analysis
Authors: Guilherme Moraes Balbim, Ryan S Falck, Cindy K Barha, Samantha Y Starkey, Alexis Bullock, Jennifer C Davis, Teresa Liu-Ambrose
Journal: British Journal of Sports Medicine (2022)

Objectives To assess the effect of exercise training on the cognitive function of older adults living with different types of dementia, as well as potential moderators of exercise efficacy. Design Systematic review and meta-analysis. Data sources Cochrane Central, PsycINFO, Embase, Medline and CINAHL. Eligibility criteria Peer-reviewed, randomised controlled trials, in English (1990–present), which examined the effects of exercise training on the cognitive function of older adults living with dementia. Study appraisal and synthesis Risk of bias and study quality were assessed (Cochrane Risk of Bias Tool 2.0 and Physiotherapy Evidence Database Scale). We performed random-effects models using robust variance estimation and tested moderators using the approximate Hotelling-Zhang test. Results Twenty-eight studies (n=2158) were included in the qualitative review and 25 in the meta-analysis. For all-cause dementia, a small effect of exercise training on cognitive function was observed ( g =0.19; 95% CI 0.05 to 0.33; p=0.009). Type of dementia and exercise training characteristics did not moderate the effects of exercise training on cognitive function (p&gt;0.05). Adherence to the intervention moderated the cognitive outcome effect size such that greater mean adherence was associated with greater cognitive outcome effect sizes ( b =0.02; SE =0.01; p=0.005). Conclusion Exercise training showed small benefits for the cognitive function of older adults living with all-cause dementia. More research and standardised reporting of exercise training characteristics can strengthen the evidence for what works best for which types of dementia. PROSPERO registration number CRD42020198716.
Cancer Immunoediting in the Era of Immuno-oncology
Authors: Matthew M. Gubin, Matthew D. Vesely
Journal: Clinical Cancer Research (2022)

Abstract Basic science breakthroughs in T-cell biology and immune–tumor cell interactions ushered in a new era of cancer immunotherapy. Twenty years ago, cancer immunoediting was proposed as a framework to understand the dynamic process by which the immune system can both control and shape cancer and in its most complex form occurs through three phases termed elimination, equilibrium, and escape. During cancer progression through these phases, tumors undergo immunoediting, rendering them less immunogenic and more capable of establishing an immunosuppressive microenvironment. Therefore, cancer immunoediting integrates the complex immune–tumor cell interactions occurring in the tumor microenvironment and sculpts immunogenicity beyond shaping antigenicity. However, with the success of cancer immunotherapy resulting in durable clinical responses in the last decade and subsequent emergence of immuno-oncology as a clinical subspecialty, the phrase “cancer immunoediting” has recently, at times, been inappropriately restricted to describing neoantigen loss by immunoselection. This focus has obscured other mechanisms by which cancer immunoediting modifies tumor immunogenicity. Although establishment of the concept of cancer immunoediting and definitive experimental evidence supporting its existence was initially obtained from preclinical models in the absence of immunotherapy, cancer immunoediting is a continual process that also occurs during immunotherapy in human patients with cancer. Herein, we discuss the known mechanisms of cancer immunoediting obtained from preclinical and clinical data with an emphasis on how a greater understanding of cancer immunoediting may provide insights into immunotherapy resistance and how this resistance can be overcome.
Intrahepatic inflammatory IgA<sup>+</sup>PD-L1<sup>high</sup> monocytes in hepatocellular carcinoma development and immunotherapy
Authors: Pil Soo Sung, Dong Jun Park, Pu Reun Roh, Kyoung Do Mun, Sung Woo Cho, Gil Won Lee, Eun Sun Jung, Sung Hak Lee, Jeong Won Jang, Si Hyun Bae, Jong Young Choi, Jonghwan Choi, Jaegyoon Ahn, Seung Kew Yoon
Journal: Journal for ImmunoTherapy of Cancer (2022)

Background IgA neutralizes pathogens to prevent infection at mucosal sites. However, emerging evidence shows that IgA contributes to aggravating inflammation or dismantling antitumor immunity in human diseased liver. The aim of this study was to elucidate the roles of inflammation-induced intrahepatic inflammatory IgA + monocytes in the development of hepatocellular carcinoma (HCC). Methods Patient cohorts including steatohepatitis cohort (n=61) and HCC cohort (n=271) were established. Patients’ surgical and biopsy specimens were analyzed using immunohistochemistry. Multicolor flow cytometry was performed with a subset of patient samples. Single-cell RNA-Seq analysis was performed using Gene Expression Omnibus (GEO) datasets. Additionally, we performed in vitro differentiation of macrophages, stimulation with coated IgA, and RNA sequencing. Hepa1-6 cells and C57BL/6N mice were used to obtain HCC syngeneic mouse models. Results Serum IgA levels were associated (p&lt;0.001) with fibrosis progression and HCC development in patients with chronic liver diseases. Additionally, immunohistochemical staining of inflamed livers or HCC revealed IgA positivity in monocytes, with a correlation between IgA + cell frequency and IgA serum levels. Compared with IgA − monocytes, intrahepatic IgA + monocytes expressed higher levels of programmed death-ligand 1 (PD-L1) in inflamed livers and in HCC tumor microenvironment. Single-cell RNA sequencing using NCBI GEO database indicated an upregulation in inflammation-associated genes in the monocytes of patients whose plasma cell IGHA1 expression was greater than or equal to the median value. Bulk RNA sequencing demonstrated that in vitro stimulation of M2-polarized macrophages using coated IgA complex induced PD-L1 upregulation via YAP-mediated signaling. In vivo blockade of IgA signaling decreased the number of tumor-infiltrating IgA + PD-L1 high macrophages and increased the number of CD69 + CD8 + T cells to enhance antitumor effects in HCC mice models. Conclusions Overall, the findings of this study showed that serum IgA levels was correlated with intrahepatic and intratumoral infiltration of inflammatory IgA + PD-L1 high monocytes in chronic liver diseases and HCC, providing potential therapeutic targets.
Balancing the risks and benefits is essential for reaping the success of adding in-circuit bacterial filters
Authors: Sven Stieglitz, Mohanchandra Mandal, Pradipta Bhakta, Antonio M. Esquinas
Journal: European Respiratory Journal (2022)

We read the innovative study by Rabec et al . [1] with great interest, in which they evaluated the impact of use of different inline bacterial filters on the performance of non-invasive ventilator (NIV) using positive inspiratory pressure (PIP) ventilation. After analysing the study, we want to raise some points which are vital in interpreting the outcomes of this study. Balancing the benefits and drawbacks is essential to extract the advantages of adding an inline bacterial filter during non-invasive ventilation <https://bit.ly/3JDHjwL>
Venetoclax combined with <scp>FLAG‐IDA</scp> induction and consolidation in newly diagnosed acute myeloid leukemia
Authors: Courtney D. DiNardo, Curtis A. Lachowiez, Koichi Takahashi, Sanam Loghavi, Tapan Kadia, Naval Daver, Lianchun Xiao, Maria Adeoti, Nicholas J. Short, Koji Sasaki, Sa A. Wang, Gautam Borthakur, Ghayas Issa, Abhishek Maiti, Yesid Alvarado, Naveen Pemmaraju, Guillermo Montalban Bravo, Lucia Masarova, Musa Yilmaz, Nitin Jain, Michael Andreeff, Guillermo Garcia‐Manero, Steven Kornblau, Farhad Ravandi, Elias Jabbour, Marina Y. Konopleva, Hagop M. Kantarjian
Journal: American Journal of Hematology (2022)

Abstract Multi‐agent induction chemotherapy (IC) improves response rates in younger patients with acute myeloid leukemia (AML); however, relapse remains the principal cause of treatment failure. Improved induction regimens are needed. A prospective single‐center phase Ib/II study evaluating fludarabine, cytarabine, G‐CSF, and idarubicin combined with venetoclax (FLAG‐IDA + VEN) in patients with newly diagnosed (ND) or relapsed/refractory AML. The primary efficacy endpoint was assessment of overall activity (overall response rate [ORR]: complete remission [CR] + CR with partial hematologic recovery [CRh] + CR with incomplete hematologic recovery [CRi] + morphologic leukemia free state + partial response). Secondary objectives included additional assessments of efficacy, overall survival (OS), and event‐free survival (EFS). Results of the expanded ND cohort with additional follow‐up are reported. Forty‐five patients (median age: 44 years [range 20–65]) enrolled. ORR was 98% ( N = 44/45; 95% credible interval 89.9%–99.7%). Eighty‐nine percent ( N = 40/45) of patients attained a composite CR (CRc + CRh + CRi) including 93% ( N = 37/40) who were measurable residual disease (MRD) negative. Twenty‐seven (60%) patients transitioned to allogeneic stem cell transplant (alloHSCT). Common non‐hematologic adverse events included febrile neutropenia (44%; N = 20), pneumonia (22%, N = 10), bacteremia (18%, N = 8), and skin/soft tissue infections (44%, N = 20). After a median follow‐up of 20 months, median EFS and OS were not reached. Estimated 24‐month EFS and OS were 64% and 76%, respectively. FLAG‐IDA + VEN is an active regimen in ND‐AML capable of producing high MRD‐negative remission rates and enabling transition to alloHSCT when appropriate in most patients. Toxicities were as expected with IC and were manageable. Estimated 24‐month survival appears favorable compared to historical IC benchmarks.